Modify. Intensify. Amplify.
As biopharmaceutical manufacturers and CDMOs face growing pressure to increase throughput and lower costs in order to stay competitive, process intensification (PI) seems the natural solution – but many feel implementing that level of change is an unrealistic expectation. Sartorius helps manufacturers balance today’s demands with tomorrow’s discoveries, intensifying key processes to experience the benefits of PI now while building for the future.
What is the Definition of Process Intensification?
Process intensification is a holistic framework to maximize overall productivity of the unit operation(s), or the manufacturing process, or the facility output for biomanufacturing.
- Enables faster drug development
- Increases the efficiency and productivity in GMP
- Applicable to any process irrespective of molecule
Benefits of Process Intensification: Key Considerations and Expert Insights
This report will discuss process intensification strategies and highlight five areas in which they can help biologics manufacturers achieve organizational goals. The report contains insights from industry leaders and experts, from pharma to CDMOs.
Producing Diverse Molecules at Various Volumes
For biopharmaceutical manufacturers to stay competitive while delivering multiple specialized products in smaller batches or blockbuster-level volumes, they must achieve the highest levels of productivity possible. Unfortunately, many are operating within existing stainless-steel facilities built for large volumes, and they cannot compete with facilities that employ single-use solutions and other intensified technologies.
Concentrated Fed-Batch Fuels Productivity
Intensifying seed train operations is one way to see immediate impact on upstream productivity.
Concentrated fed-batch enables manufacturers to achieve productivity levels up to four times that of standard fed-batch operations. Enabling concentrated fed-batch capabilities is one way Sartorius helps bring process intensification technologies into existing systems or when planning new facilities.
- The Biostat STR® single-use, perfusion enabled bioreactor manages volumes from 50 L to 2000 L and with integrated analytical and automation tools for PAT.
Manufacturing Complex Products While Controlling Costs
In the past 10 years, the average annual peak sales per molecule has decreased by 50% while average annual costs to develop each molecule increased by 30% – this introduces a mission-critical need to reduce COGS. Manufacturers that currently rely on fed-batch operations have an opportunity to introduce technologies that can quickly modify their existing upstream processes to bring larger gains in productivity and ultimately reduce production costs.
N-1 Supercharges the Seed Train to Bring Costs Down
Implementing N-1 perfusion in the seed train can result in a 30-50% reduction in cost/g compared to standard fed-batch operations and is a key example of process intensification. Sartorius is the only company offering two flexible N-1 seed train intensification options for rocking motion and stirred tank bioreactors along with state-of-the-art integrated analytical tools:
- The Biostat® RM rocking motion bioreactor with single-use Flexsafe® RM bags, integrated perfusion membrane and in-line analytical & automation tools.
- The perfusion enabled Biostat STR® single-use bioreactors from 50 L to 2000 L scale with integrated analytical and automation tools (additional cell retention device necessary).
- The 4Cell® XtraCHO media system optimized for CHO-DG44 cells.
Gaining Flexibility in Your Operations
As medicines become more specialized, the number of low-volume batches and variables in manufacturing processes will increase significantly. Analyses of commercial R&D pipelines between now and 2025 indicate more than 80% of candidates would require production of less than 500 kg per year to meet demand. To keep up with these trends, manufacturing operations need to manage higher throughput of individual therapies as well as accommodate different modalities within the same facility.
Intensified Bioprocessing Made Possible with CFB
Sartorius can help introduce concentrated fed-batch (CFB) technology, enabling manufacturers to achieve throughput 3-4 times higher than standard fed-batch. This supports intensified bioprocessing and the flexibility biomanufacturers require to remain competitive:
- The Biostat STR® single-use, perfusion enabled bioreactor and the Biostat® RM rocking motion bioreactor with integrated, analytical and automation tools for PAT.
Accommodating a Modular Mindset
Traditional upstream operations that rely on fed-batch processes simply cannot support the diversity of modalities resulting from innovations in protein-based medicines. Meanwhile, specialized medicines mean smaller throughput requirements, with almost 60% of drugs requiring 300 kg/year throughput or less to satisfy patient demands. Given these trends, manufactures are looking for flexible smaller modular Single Use perfusion based facilities to support this diversity in modalities and enable faster changeovers between multiple products.
Perfusion-Based Process for Modular Design
Manufacturing multiple modalities rely on introducing perfusion-based technologies that require smaller bioreactors which often results in modular facility designs. This results in a smaller footprint, lower upfront capex investment and reduced changeover times due to single-use technology implementation
- Sartorius offers intensification tools such as the Biostat® RM and Biostat® STR which fit all process types with media handling technologies and integrated, scalable analytical tools for small, single-use modular facilities.
Reducing the Time Demands of Process Development
Speed-to-market is often what determines a product’s competitive position and pricing. Selecting the right process development tools that can reduce your development timelines and establish scalable flexible processes becomes very critical.
Reach IND Submission Sooner With the Right Tools
Sartorius offers several solutions to accelerate IND submission by reducing time spent on process development while integrating PAT for faster process optimization. Easy scale-up to any of the different upstream intensification schemes makes this approach very flexible.
- Sartorius´ Cellca CHO Expression Platform delivers DNA to RCB within 14 weeks and RCB to MCB in five months. With no media or process optimization required from small to large scale for cell line, media and scalable upstream processes, manufacturers can save up to two months in development.
- Sartorius’ high throughput Ambr® systems along with PAT integration allow faster process optimization. The Ambr 15 Cell culture system is the smallest single-use bioreactor which can mimic perfusion culture at 15 mL volume to optimize the selection of cell line and media. While Ambr 250 perfusion system is an ideal scale-down process development/characterization system.
PI Interview Series
Why is the Biomanufacturing Industry Moving Towards Process Intensification?
Miriam Monge talks about the significance of intensified and continuous processing, the importance of the arrival of biosimilars on the market, and exciting Sartorius developments in the commercial biomanufacturing industry.
The Changing Landscape of Single-Use Technologies and Process Intensification
The industry is redefining regulatory and industry standards due to the implementation of single-use technologies. How does this affect the benefits of process intensification? Watch Miriam Monge in discussion with Dan Stanton, Editor of Bioprocess Insider.
Single-Use and Process Intensification in Commercial Biomanufacturing
How do single-use facilities influence cost of goods, flexibility, and reduced footprint in biopharmaceutical manufacturing and how does process intensification play a role? Watch Gerben Zijlstra in discussion with Dan Stanton, Editor of Bioprocess Insider.